Pharmacology - Drug Development (part 2)

Clinical testing starts with Phase I studies on healthy subjects and seeks to determine whether effects observed in animal experiments also occur in humans. Dose-response relationships are determined. In Phase II, potential drugs are first tested on selected patients for therapeutic efficacy in those disease states for which they are intended.

Should a beneficial action be evident and the incidence of adverse effects be
acceptably small, Phase III is entered, involving a larger group of patients in
whom the new drug will be compared with standard treatments in terms of therapeutic outcome. As a form of human experimentation, these clinical trials are subject to review and approval by institutional ethics committees according to international codes of conduct (Declarations of Helsinki, Tokyo and Venice). During clinical testing, many drugs are revealed to be unusable. Ultimately, only one new drug remains from approximately 10,000 newly synthesized substances. The decision to approve a new drug is made by a national regulatory body (Food & Drug Administration in the U.S.A., the Health Protection Branch Drugs Directorate in Canada, UK, Europe, Australia) to which manufacturers are required to submit their applications. Applicants must document by means of appropriate test data (from preclinical and clinical trials) that the criteria of efficacy and safety have been
met and that product forms (tablet, capsule, etc.) satisfy general standards of quality control.

Following approval, the new drug may be marketed under a trade name
(p. 333) and thus become available for prescription by physicians and dispensing by pharmacists. As the drug gains more widespread use, regulatory surveillance continues in the form of post-licensing studies (Phase IV of clinical trials). Only on the basis of long-term experience will the risk: benefit ratio be properly assessed and, thus, the therapeutic value of the new drug be determined.

Pharmacology - Drug Development (part 1)

This process starts with the synthesis of novel chemical compounds. Substances with complex structures may be obtained from various sources, e.g., plants (cardiac glycosides), animal tissues (heparin), microbial cultures (penicillin G), or human cells (urokinase), or by means of gene technology (human insulin). As more insight is gained into structure-activity relationships, the search for new agents becomes more clearly focused.

Preclinical testing yields information on the biological effects of new substances. Initial screening may employ

biochemical-pharmacological investigations (e.g., receptor-binding assays p. 56) or experiments on cell cultures, isolated cells, and isolated organs. Sincethese models invariably fall short of replicating complex biological processes in the intact organism, any potential drug must be tested in the whole animal. Only animal experiments can reveal whether the desired effects will actually occur at dosages that produce little or no toxicity. Toxicological investigations serve to evaluate the potential for:

(1) toxicity associated with acute or chronic administration;

(2) genetic damage (genotoxicity, mutagenicity);

(3) production of tumors (onco- or carcinogenicity);

(4) causation of birth defects (teratogenicity).

In animals, compounds under investigation also have to be studied with respect to their absorption, distribution, metabolism, and elimination (pharmacokinetics). Even at the level of preclinical testing, only a very small fraction of new compounds will prove potentially fit for use in humans. Pharmaceutical technology provides the methods for drug formulation.

Pharmacology History - Today (Status Quo)

After 1920, pharmacological laboratories sprang up in the pharmaceutical industry, outside established university institutes. After 1960, departments of clinical pharmacology were set up at many universities and in industry.

Drug and Active Principle

Until the end of the 19th century, medicines were natural organic or inorganic products, mostly dried, but also fresh, plants or plant parts. These might contain substances possessing healing (therapeutic) properties or substances exerting a toxic effect. In order to secure a supply of medically useful products not merely at the
time of harvest but year-round, plants were preserved by drying or soaking them in vegetable oils or alcohol.

Drying the plant or a vegetable or animal product yielded a drug (from French “drogue” – dried herb). Colloquially, this term nowadays often refers to chemical substances with high potential for physical dependence and abuse. Used scientifically, this term implies nothing about the quality of action, if any. In its original, wider sense, drug could refer equally well to the dried leaves of peppermint, dried lime blossoms, dried flowers and leaves of the female cannabis plant (hashish, marijuana), or the dried milky exudate obtained by slashing the unripe seed capsules of Papaver somniferum (raw opium). Nowadays, the term is applied quite generally to a chemical substance that is used for pharmacotherapy. Soaking plants parts in alcohol (ethanol) creates a tincture. In this process, pharmacologically active constituents of the plant are extracted by the alcohol. Tinctures do not contain the complete spectrum of substances that exist in the plant or crude drug, only those that are soluble in alcohol. In the case of opium tincture, these ingredients are alkaloids (i.e., basic substances of plant origin) including: morphine, codeine, narcotine = noscapine, papaverine, narceine, and others. Using a natural product or extract to treat a disease thus usually entails the
administration of a number of substances possibly possessing very different activities. Moreover, the dose of an individual constituent contained within a given amount of the natural product is subject to large variations, depending upon the product‘s geographical origin (biotope), time of harvesting, or conditions and length of storage. For the same reasons, the relative proportion of individual constituents may vary considerably.
Starting with the extraction of morphine from opium in 1804 by F. W. Sertürner (1783–1841), the active principles of many other natural products were subsequently isolated in chemically pure form by pharmaceutical laboratories.

The aims of isolating active principles are:
1. Identification of the active ingredient(s).
2. Analysis of the biological effects (pharmacodynamics) of individual ingredients and of their fate in the body
(pharmacokinetics).
3. Ensuring a precise and constant dosage in the therapeutic use of chemically pure constituents.
4. The possibility of chemical synthesis, which would afford independence from limited natural supplies and create conditions for the analysis of structure-activity relationships. Finally, derivatives of the original constituent may be synthesized in an effort to optimize pharmacological properties. Thus, derivatives of the original constituent with improved therapeutic usefulness may be developed.

Pharmacology History - Recognition

Oswald Schmiedeberg (1838–1921), together with his many disciples (12 of whom were appointed to chairs of pharmacology), helped to establish the high reputation of pharmacology. Fundamental concepts such as structure-activity relationship, drug receptor, and selective toxicity emerged from the work of, respectively, T. Frazer (1841–1921) in Scotland, J. Langley (1852–1925) in England, and P. Ehrlich (1854–1915) in Germany. Alexander J. Clark (1885–1941) in England first formalized receptor theory in the early 1920s by applying the Law of Mass Action to drug-receptor interactions. Together with the internist, Bernhard Naunyn (1839–1925), Schmiedeberg founded the first journal of pharmacology, which has since been published without interruption. The “Father of American Pharmacology”, John J. Abel (1857–1938) was among the first
Americans to train in Schmiedeberg‘s laboratory and was founder of the Journal of Pharmacology and Experimental Therapeutics (published from 1909 until the present).

Pharmacology History - Foundation

Rudolf Buchheim (1820–1879) founded the first institute of pharmacology at the University of Dorpat (Tartu, Estonia) in 1847, ushering in pharmacology as an independent scientific discipline. In addition to a description of effects, he strove to explain the chemical properties of drugs.


“The science of medicines is a theoretical, i.e., explanatory, one. It is to provide us with knowledge by which our judgement about the utility of medicines can be validated at the bedside.”

Pharmacology History - The Early Begining

Johann Jakob Wepfer (1620–1695) was the first to verify by animal experimentation assertions about pharmacological or toxicological actions.

“I pondered at length. Finally I resolved to clarify the matter by experiments.”

Pharmacology History - The Impetus

Theophrastus von Hohenheim (1493–1541 A.D.), called Paracelsus, began to quesiton doctrines handed down from antiquity, demanding knowledge of the active ingredient(s) in prescribed remedies, while rejecting the irrational concoctions and mixtures of medieval medicine.

He prescribed chemically defined substances with such success that professional enemies had him prosecuted
as a poisoner. Against such accusations, he defended himself with the thesis that has become an axiom of pharmacology:

“If you want to explain any poison properly, what then isn‘t a poison? All things are poison, nothing is without poison; the dose alone causes a thing not to be poison.”

Pharmacology History - The Idea

Medicaments have been used for treating disease in humans and animals. The herbals of antiquity describe the therapeutic powers of certain plants and minerals. Belief in the curative powers of plants and certain substances rested exclusively upon traditional knowledge, that is, empirical information not subjected to critical examination.

Claudius Galen (129–200 A.D.) first attempted to consider the theoretical background of pharmacology. Both theory and practical experience were to contribute equally to the rational use of medicines through interpretation of observed and experienced results.

“The empiricists say that all is found by experience. We, however, maintain that it is found in part by experience, in part by theory. Neither experience nor theory alone is apt to discover all.”

US Group sues Bayer over multivitamin claims

A U.S. public advocacy group has sued Bayer AG over the company's prostate cancer marketing claims for the drugmaker's One A Day multivitamin for men.


The suit, filed by the Center for Science in the Public Interest (CSPI) on September 30 and announced on Thursday, challenges Bayer's promotion of the vitamin's selenium ingredient as a way to "support prostate health" and "reduce the risk of prostate cancer."

Such claims were made on the drugmaker's website, advertising and product label, the group said.
The suit, filed in Superior Court in San Francisco, said such claims are false because selenium -- a trace mineral -- "may actually cause harm to consumers," CSPI said in its lawsuit.
Representatives for Bayer had no immediate commen

Pharmacy Images around the world

Pharmacy images around the world:

What is pharmacy?

Pharmacy (from the Greek φάρμακον 'pharmakon' = drug) is the health profession that links the health sciences with the chemical sciences, and it is charged with ensuring the safe and effective use of medication.

The scope of pharmacy practice includes more traditional roles such as compounding and dispensing medications, and it also includes more modern services related to patient care, including clinical services, reviewing medications for safety and efficacy, and providing drug information. Pharmacists, therefore, are the experts on drug therapy and are the primary health professionals who optimize medication use to provide patients with positive health outcomes. Pharmacy is also the term for an establishment where pharmacy (in the first sense) is practised (synonym: drugstore). The first pharmacy in Europe (still working) was opened in 1241 in Trier, Germany.

The word pharmacy is derived from its root word pharma which was a term used since the 1400–1600s. In addition to pharma responsibilities, the pharma offered general medical advice and a range of services that are now performed solely by other specialist practitioners, such as surgery and midwifery. The pharma (as it was referred to) often operated through a retail shop which, in addition to ingredients for medicines, sold tobacco and patent medicines. The pharmas also used many other herbs not listed.

In its investigation of herbal and chemical ingredients, the work of the pharma may be regarded as a precursor of the modern sciences of chemistry and pharmacology, prior to the formulation of the scientific method.

Disciplines of Pharmacy

The field of Pharmacy can generally be divided into three primary disciplines:

* Pharmaceutics
* Medicinal chemistry and Pharmacognosy
* Pharmacy practice

The boundaries between these disciplines and with other sciences, such as biochemistry, are not always clear-cut; and often, collaborative teams from various disciplines research together.

Pharmacology is sometimes considered a fourth discipline of pharmacy. Although pharmacology is essential to the study of pharmacy, it is not specific to pharmacy. Therefore it is usually considered to be a field of the broader sciences.

Other specializations in pharmacy practice recognized by the Board of Pharmaceutical Specialties include: cardiovascular, infectious disease, oncology, pharmacotherapy, nuclear, nutrition, and psychiatry.[1] The Commission for Certification in Geriatric Pharmacy certifies pharmacists in geriatric pharmacy practice. The American Board of Applied Toxicology certifies pharmacists and other medical professionals in applied toxicology.

History of Pharmacy

Paleopharmacological studies attest to the use of medicinal plants in pre-history.

The earliest known compilation of medicinal substances was ARIANA the Sushruta Samhita, an Indian Ayurvedic treatise attributed to Sushruta in the 6th century BC. However, the earliest text as preserved dates to the 3rd or 4th century AD.

Many Sumerian (late 6th millennium BC - early 2nd millennium BC) cuneiform clay tablets record prescriptions for medicine.

Ancient Egyptian pharmacological knowledge was recorded in various papyri such as the Ebers Papyrus of 1550 BC, and the Edwin Smith Papyrus of the 16th century BC.

The earliest known Chinese manual on materia medica is the Shennong Bencao Jing (The Divine Farmer's Herb-Root Classic), dating back to the 1st century AD. It was compiled during the Han dynasty and was attributed to the mythical Shennong. Earlier literature included lists of prescriptions for specific ailments, exemplified by a manuscript "Recipes for 52 Ailments", found in the Mawangdui tomb, sealed in 168 BC. Further details on Chinese pharmacy can be found in the Pharmacy in China article.